6-Sulfanilamidoindazole (6-SAI) is an orally administered antibacterial sulfonamide which induces arthritis and periarthritis in the ankles and hind paws of aged rats. The mechanisms involved in the pathogenesis of inflammation are unknown. The working hypothesis in the research proposal is that arthritis in 6-SAI treated rats is caused by at least two events which are: (1) the elevations in plasma fibrinogen concentration; (2) introduction of endotoxin or an endotoxin like material from the gut which triggers microclot formation and the deposition of these clots in the ankles and paws where they initiate inflammation. To test this hypothesis six groups of experiments will be performed. They are: (1) to study the effects of 6-SAI on fibrinogen synthesis in vitro; (2) to evaluate the role of the gastrointestinal flora in the pathogenesis of inflammation: (3) induction of arthritis in hyperfibrinogenemic rats with endotoxin; (4) demonstration of fibrinogen-fibrin material in joints; (5) suppression of arthritis by immunization with endotoxin and induction of hypofibrinogenemia; and, (6) evaluation of the role of stasis of blood in the pathogenesis of arthritis.